Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction by Biomarkers (DETO2X-bio)

December 8, 2017 updated by: Leif Svensson, Karolinska Institutet

Determination of the Role of Oxygen on Mechanisms Involved in Ischemia-reperfusion Injury in Suspected Acute Myocardial Infarction by Biomarkers. A Sub Study to the DETO2X-AMI Trial.

Oxygen treatment is widely used in acutely ill patients, both pre-hospital and in hospital. The indication for oxygen is sometimes unquestionable, such as in many hypoxic patients, but in other situations its use is more of a practise and much less based on scientific evidence. In particular, oxygen treatment is routinely used in patients with a suspected heart attack and variably recommended in guidelines, despite very limited data supporting a beneficial effect. Indeed, a few studies even indicate that oxygen treatment might be harmful.

Immediate re-opening of the acutely blocked artery to the heart muscle is the treatment of choice to limit permanent injury. However, the sudden re-initiation of blood flow achieved with primary percutaneous coronary intervention (PCI), the reopening and stenting of the blocked vessel, can give rise to further endothelial and myocardial damage, so-called reperfusion injury. Ischemia and reperfusion associated myocardial injury (IR-injury) involves a wide range of pathological processes. Vascular leakage, activation of cell death programs, thrombocytes and white blood cells leading to extended inflammation and formation of clots are examples of those effects.

The role of oxygen treatment on these pathological processes, on the extent of IR-injury and the final infarct size in patients with acute myocardial infarctions (AMI) has not previously been studied.

In an ongoing national multicentre, randomized, registry based clinical trial, the DETO2X-AMI trial (NCT01787110), the effect of oxygen on morbidity and mortality in ACS patients is being investigated.

The present DETO2X-biomarkers study is a substudy of the DETO2X-AMI trial, evaluating the effect of oxygen treatment on biological systems involved in the pathogenesis of reversible and irreversible myocardial damage and cell death in ACS.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The DETermination of the role of OXygen i suspected Acute Myocardial Infarction (DETO2X-AMI) trial (NCT01787110), an ongoing multicentre, randomized, registry based clinical trial, is investigating the effect of oxygen on morbidity and mortality in ACS patients.

The present DETO2X-biomarkers study is a substudy of the DETO2X-AMI trial, evaluating the effect of oxygen treatment on biological systems involved in the pathogenesis of reversible and irreversible myocardial damage and cell death in ACS.

AIMS

To evaluate the effect of oxygen treatment on markers of oxidative stress in ACS patients. To assess the effect of oxygen treatment on soluble markers of apoptosis, MMPs and TIMPs in ACS patients.

To study the effect of oxygen treatment on systemic inflammatory activity and leukocyte activation.

To evaluate the effect of oxygen treatment on platelet activation in ACS patients.

HYPOTHESIS

The main hypothesis is that oxygen treatment enhances oxidative stress, systemic inflammation, and markers of apoptosis and MMPs in ACS patients, thereby potentially increasing myocardial damage and cell death, and worsening the prognosis.

STUDY DESIGN and POPULATION

The present study is a biomarker substudy of the DETO2X-AMI trial. The design and population of the DETO2X-AMI trial has previously been described in detail (NCT01787110). All patients included in the DETO2X-AMI trial at Södersjukhuset Stockholm and University Hospital Linköping during the study period specified below are also eligible to be included in the DETO2X-biomarkers study. We intend to include 150 patients with suspected AMI.

STUDY PLAN

All study participants in the DETO2X-biomarkers study have been allocated to receive oxygen (6L/min) or no oxygen treatment as part of the DETO2X-AMI trial. To a variable degree, the participants have already started this treatment when entering the biomarker substudy. Baseline blood samples will be collected as soon as possible after inclusion in the DETO2X-AMI trial, preferably prior to initiation of oxygen treatment. Study subjects will then continue to receive their allocated DETO2X-AMI study treatment. A second set of blood samples will be collected 5-7 hours after randomisation in the DETO2X-AMI trial, and always prior to discontinuation of oxygen treatment.

ANALYSIS of blood samples

As a marker of oxidative stress, plasma-isoprostane will be measured using gas chromatography combined with a massspectrometric detector. Soluble markers of apoptosis, MMP-2 and TIMP-2 will be analyzed by Luminex. Plasma inflammatory markers (C-reactive protein (CRP) and interleukin (IL)-6), myeloperoxidase, and markers of platelet activation will be analysed by ELISA. Flow cytometry will be used to analyse neutrophil integrin receptors and platelet-leukocyte aggregates in whole blood. Whole blood will be fixated and red blood cells lysed before analysis.

EFFICACY OUTCOME

To determine the effect of oxygen treatment on biomarkers of oxidative stress, apoptosis, matrix metalloproteinases, markers of inflammation, and leukocyte and platelet activation in patients admitted to hospital due to suspected AMI.

SUMMARY

The DETO2X-AMI trial will address the effects of oxygen on morbidity and mortality in ACS patients. The present DETO2X-biomarkers substudy is evaluating effects of oxygen treatment on biological systems involved in the pathogenesis of reversible and irreversible myocardial damage and cell death in ACS and may add essential new knowledge to the mechanistics of ischaemic myocardial injury.

Study Type

Interventional

Enrollment (Actual)

175

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Linköping, Sweden, 58191
        • Linköping University Hospital
      • Stockholm, Sweden, 11883
        • Södersjukhuset

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • symptoms (chest pain, dyspnea) indicating acute myocardial ischemia within the last 6 hours
  • ECG changes (ST-segment elevation ≥ 2 mm V1-V4, or ≥ 1 mm in other leads, ST-segment depression >1 mm in any lead, negative T-wave in leads V2-V6, pathological Q-wave in at least 2 adjacent leads), left bundle branch block

and/or elevated levels of cardiac troponin levels in the emergency department indicating acute myocardial ischemia

  • oxygen saturation ≥90% (pulse oximeter)
  • age ≥30

Exclusion Criteria:

  • unwillingness to participate
  • inability to comprehend given information
  • continuous oxygen delivery at home prior to inclusion
  • cardiac arrest prior to inclusion

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oxygen

For patients randomized to oxygen therapy:

  • 6 L/min of oxygen delivered by oxymask® started immediately after inclusion of the ambulance service or in the emergency department given continuously for 6-12 hours (at least 6 hours)
  • all patients receive standard acute coronary syndrome treatment including reperfusion strategies
Drug: Oxygen
see arm description
No Intervention: No oxygen

For patients randomized to withholding oxygen treatment

  • no oxygen is administered at any time as long as the oxygen saturation is ≥90% on pulse oximeter (repetitive checks are performed)
  • all patients receive standard acute coronary syndrome treatment including reperfusion strategies
  • observation duration 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma concentration levels over time of biomarkers of oxidative stress, apoptosis, inflammation and platelet aggregation
Time Frame: Within 8hours from baseline

Venous blood samples will be collected at baseline and 5-7 hours after baseline. Plasma concentration levels will be analyzed for Interleukin (IL)-6 [pg/mL], CRP [mg/L], Isoprostane [pg/mL], Soluble TNF receptor 1 [pg/mL], Soluble TNF receptor 2 [pg/mL], Soluble Fas [pg/mL], Soluble Fas ligand (pg/mL], MMP-2 [ng/mL], TIMP-2 [ng/mL], Soluble P-selectin [ng/mL], Platelet factor (PF)-4 [ng/mL], Beta-thromboglobulin [ng/mL].

Optional, flow cytometry will be used to analyse neutrophil integrin receptors (CD11b/CD18) and platelet-leukocyte aggregates (CD41a/CD11b/CD45) in whole blood. Whole blood will be fixated and red blood cells lysed before analysis.
Within 8hours from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Collaborators

University Hospital, Linkoeping

Investigators

  • Principal Investigator: Lennart Lennart, MD, PHD, Department of Medical and Health Sciences, Linköping University, and Department of Cardiology, University Hospital, 58185 Linköping, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2014

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

November 8, 2014

First Submitted That Met QC Criteria

November 8, 2014

First Posted (Estimate)

November 13, 2014

Study Record Updates

Last Update Posted (Actual)

December 11, 2017

Last Update Submitted That Met QC Criteria

December 8, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DETO2X-biomarkers 2012/287-12

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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